PAX6 is a useful marker for pancreatic origin of neuroendocrine neoplasms: A tissue microarray study evaluating more than 19,000 tumors from 150 different tumor types

Florian Lutz; Sophie-Marie Hornburg; Katharina Möller; Florian Viehweger; Ria Schlichter; Anne Menz; Andreas M Luebke; Martina Kluth; Claudia Hube-Magg; Andrea Hinsch; Maximilian Lennartz; Christian Bernreuther; Sören Weidemann; Patrick Lebok; Christoph Fraune; Guido Sauter; David Dum; Andreas H Marx; Ronald Simon; Natalia Gorbokon; Eike Burandt; Sarah Minner; Stefan Steurer; Till Krech; Frank Jacobsen; Till S Clauditz

doi:10.1016/j.humpath.2024.105695

PAX6 is a useful marker for pancreatic origin of neuroendocrine neoplasms: A tissue microarray study evaluating more than 19,000 tumors from 150 different tumor types

Hum Pathol. 2024 Nov 19:105695. doi: 10.1016/j.humpath.2024.105695. Online ahead of print.

Authors

Florian Lutz¹, Sophie-Marie Hornburg¹, Katharina Möller¹, Florian Viehweger¹, Ria Schlichter¹, Anne Menz¹, Andreas M Luebke¹, Martina Kluth¹, Claudia Hube-Magg¹, Andrea Hinsch¹, Maximilian Lennartz¹, Christian Bernreuther¹, Sören Weidemann¹, Patrick Lebok², Christoph Fraune², Guido Sauter¹, David Dum¹, Andreas H Marx³, Ronald Simon⁴, Natalia Gorbokon¹, Eike Burandt¹, Sarah Minner¹, Stefan Steurer¹, Till Krech², Frank Jacobsen¹, Till S Clauditz¹

Affiliations

¹ Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
² Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany.
³ Department of Pathology, Academic Hospital Fuerth, Fuerth Germany.
⁴ Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: R.Simon@uke.de.

PMID: 39571690
DOI: 10.1016/j.humpath.2024.105695

Abstract

PAX6 immunohistochemistry (IHC) was proposed as a tool to identify a pancreatic origin of neuroendocrine neoplasms (NENs). To evaluate the diagnostic utility of PAX6 IHC, a tissue microarray containing 19,214 samples from 150 tumor types was analyzed. Data on progesterone receptor (PR) and glutamate decarboxylase 2 (GAD2) expression were available from previous studies. PAX6 staining occurred in 2.6% of 17,224 analyzable tumors and 60 tumor categories showed PAX6 positivity in at least one case. The highest rates of PAX6 positivity occurred in pancreatic (42.9-70.8%) and other NENs (up to 50.0%), testicular tumors (up to 58.3%), basal cell carcinomas of the skin (51.9%), squamous cell carcinomas of different organs (1.5-11.8%), and in gynecological tumors (up to 30%). For detection of pancreatic origin of NENs, sensitivity was highest for PAX6 (68.7%) followed by GAD2 (62.6%) and PR (52.5%) while specificity was highest for GAD2 (95.2%), followed by PR (91.3%), and PAX6 (91.1%). Of the analyzed combinations, the highest sensitivity (53.8%) and specificity (100%) was found for PAX6/GAD2, although combinations of PAX6/PR (49.5%/99.3%), PR/GAD2 (40.7%/98.9%), and PAX6/PR/GAD2 (40.6%/100%) did also result in high specificity. Only 14% of the 118 NENs with negativity for all three antibodies were of pancreatic origin. It is concluded that PAX6 IHC is useful to identify a pancreatic origin in case of NEN metastases of unknown origin. The combination with GAD2 and PR further increase the diagnostic performance of PAX6 and results in a >98% specificity in case of positivity for at least 2 of these markers.